..This integrated understanding is leading to the development of a number of exciting and bold approaches to treat cancer and other diseases. But owing to several unanswered questions, caution is needed...

..Our study provides insight into different mechanisms of action of this class of drugs in recurrent glioblastoma patients and suggests that the timing of combination therapy may be critical for optimizing activity against this tumor...

..These other proangiogenic signals are functionally implicated in the revascularization and regrowth of tumors in the evasion phase, as FGF blockade impairs progression in the face of VEGF inhibition...

..Normalization of the abnormal vasculature can facilitate drug delivery to tumors and formation of a mature vasculature can help realize the promise of therapeutic angiogenesis and tissue engineering...

..Thus, vascular normalization may contribute to the improved survival rates in tumor-bearing animals and in colorectal carcinoma patients treated with an anti-VEGF antibody in combination with cytotoxic therapies...

Macrophages regulate the angiogenic switch in a mouse model of breast cancer

..Therapeutic angiogenesis (promoting new vessel growth to treat ischaemic disorders) is an exciting frontier of cardiovascular medicine, but further understanding of the mechanisms of vascular morphogenesis is needed first...

..These characteristics mean that tumor blood flow is suboptimal, resulting in hypoxia and further VEGF production. This central role of VEGF in the production of tumor vasculature makes it a rational target for anticancer therapy...

Role of tumor-associated macrophages in tumor progression and invasion

..These studies provide evidence that the VEGF gene is regulated directly by Stat3 protein, and indicate that Stat3 represents a common molecular target for blocking angiogenesis induced by multiple signaling pathways in human cancers...

..These results establish the occurrence and biological significance of intratumoral lymphangiogenesis in breast cancer and identify VEGF-C as a molecular link between tumor lymphangiogenesis and metastasis...

..We also discuss the therapeutic implications of recent findings that specific myeloid cell populations modulate the responses of tumours to agents such as chemotherapy and some anti-angiogenic therapies...

Marco PrestaUnit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, ItalyCytokine Growth Factor Rev 16:159-78. 2005

..Indeed, several experimental evidences point to a role for FGFs in tumor growth and angiogenesis. This review will focus on the relevance of the FGF/FGF receptor system in adult angiogenesis and its contribution to tumor vascularization...

..Recent progress in the molecular and biological understanding of the VEGF/VEGFR system provides us with novel and promising therapeutic strategies and target proteins for overcoming a variety of diseases...

Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases

..These findings support that pharmacological inhibition of the enzymatic activity of the vascular endothelial growth factor receptor represents a novel strategy for limiting the growth of a wide variety of tumor types...

Metalloproteinases: role in breast carcinogenesis, invasion and metastasis

..Because MMPs are apparently involved in breast cancer initiation and dissemination, inhibition of these proteinases may be of value both in preventing breast cancer and in blocking metastasis of established tumours..

..Many of the miR changes associated with specific stages and hallmark capabilities in the mouse model are similarly altered in human tumors, including cognate pancreatic neuroendocrine tumors, implying a generality...

..Also of concern is that the expected need to use anti-angiogenic drugs chronically will lead to delayed toxic side effects in humans, which do not appear in rodents, especially in short-term studies...

..Because MAPCs can be expanded in culture without obvious senescence for more than 80 population doublings, they may be an important source of endothelial cells for cellular pro- or anti-angiogenic therapies...

..Antiproteolysis, particularly in the context of angiogenesis, has become a key target in therapeutic strategies aimed at inhibiting tumor growth and other diseases associated with neovascularization...

Expression of pro- and anti-angiogenic isoforms of VEGF is differentially regulated by splicing and growth factors

..014 and P < 0.0015, respectively). These results indicated that host-derived gelatinase A plays an important role in angiogenesis and tumor progression, suggesting the usefulness of gelatinase A inhibitors for anticancer chemotherapy...

Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors

..Our findings support the view that matrix-bound VEGF and nontethered VEGF provide different signaling outcomes. These findings reveal a novel aspect in the regulation of extracellular VEGF that holds significance for vascular patterning...

..This review intends to integrate our recent knowledge in this field into a rational strategy that could be the basis for developing effective clinical modalities using antivascular therapy for cancer...

..2-3.0-fold) in response to celecoxib. Thus, the antitumor activity of celecoxib may be attributable, at least in part, to a direct effect on host stromal elements, such as the angiogenic vasculature...

..PUBLIC HEALTH RELEVANCE: The healing of tissues after surgery or trauma is critical for long-term survival. The proposed work will study novel mechanisms by which blood vessels grow in response to tissue injury. ..

..This proposal will provide new insights into the molecular mechanisms of CCN1 activities in vivo and may foster future safer, less destructive, and more effective therapies to harness ischemia-induced neovascularization in ROP. ..

..Our continued clarification of mechanistic controls on PAI-1 gene expression may lead to new targeted therapies for diseases in which excessive or non-resolving angiogenesis is a major pathogenic feature. ..

..This proposed study has the potential to identify a novel signaling pathway in the pathogenesis of liver disease and it may validate PEDF gene therapy as a potent new agent to combat liver cancer. ..

..The EYAs represent a novel and druggable target for treating proliferative retinopathies, and an essential feature of this project is the validation of EYA as a target for anti-angiogenic drug development. ..

..Chemical compounds that inhibit EphA2 function will have potential research applications to clarify the role of EphA2 in cancer progression, which is currently not well understood, and therapeutic applications as anti-cancer agents. ..

..In this proposal we seek to better understand how endothelial cells, which line all blood vessels, control blood vessel growth, by studying a protein called CIB1, which appears to regulate endothelial cell function. ..

..Thus, understanding the molecular mechanisms controlling angiogenesis is of key significance. The knowledge gained from this research will facilitate the treatment of cardiovascular and pulmonary disease, injuries, and cancer. ..

..Furthermore, structural determination either through x-ray crystallography or cryo-electron microscopy of an Integrin/Tie complex will identify the basis for growth factor receptor-integrin signal transduction. ..

..The information from this study will not only enhance our understanding of the pathophyiosiology of tumorigenesis but also help us to develop effective therapeutic approaches for treatment of cancers. ..

..These studies elucidate novel mechanisms of angiogenesis that depend on interactions between endothelial and peri-vascular cells, and may be key to the understanding and treatment of a variety of human vascular pathologies. ..

..D., M.D., or M.D./Ph.D. degrees. The BIDMC and Harvard Medical School have a strong commitment to the recruitment, retention, and encouragement of under-represented minorities, the disabled and individuals from disadvantaged backgrounds. ..

..V. In specific aim # 5, the characterization of fenestrated endothelia from diaphragmatic capillaries, e.g., peritubular capillaries will be carried out by utilizing the techniques described in above specific aims. ..

..Understanding the molecular mechanisms that control skin and tumor angiogenesis will be the basis for the development of novel therapeutic approaches to treat inflammatory skin diseases and skin cancer. ..